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The antidiabetic drug metformin acts on the bone microenvironment to promote myeloma cell adhesion to preosteoblasts and increase myeloma tumour burden in vivo
Multiple myeloma is a haematological malignancy that is dependent upon interactions within the bone microenvironment to drive tumour growth and osteolytic bone disease. Metformin is an anti-diabetic drug that has attracted attention due to its direct antitumor effects, including anti-myeloma propert...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8665410/ https://www.ncbi.nlm.nih.gov/pubmed/34890968 http://dx.doi.org/10.1016/j.tranon.2021.101301 |
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author | Gámez, Beatriz Morris, Emma V. Olechnowicz, Sam W.Z. Webb, Siobhan Edwards, James R. Sowman, Aneka Turner, Christina J. Edwards, Claire M. |
author_facet | Gámez, Beatriz Morris, Emma V. Olechnowicz, Sam W.Z. Webb, Siobhan Edwards, James R. Sowman, Aneka Turner, Christina J. Edwards, Claire M. |
author_sort | Gámez, Beatriz |
collection | PubMed |
description | Multiple myeloma is a haematological malignancy that is dependent upon interactions within the bone microenvironment to drive tumour growth and osteolytic bone disease. Metformin is an anti-diabetic drug that has attracted attention due to its direct antitumor effects, including anti-myeloma properties. However, the impact of the bone microenvironment on the response to metformin in myeloma is unknown. We have employed in vitro and in vivo models to dissect out the direct effects of metformin in bone and the subsequent indirect myeloma response. We demonstrate how metformin treatment of preosteoblasts increases myeloma cell attachment. Metformin-treated preosteoblasts increased osteopontin (OPN) expression that upon silencing, reduced subsequent myeloma cell adherence. Proliferation markers were reduced in myeloma cells cocultured with metformin-treated preosteoblasts. In vivo, mice were treated with metformin for 4 weeks prior to inoculation of 5TGM1 myeloma cells. Metformin-pretreated mice had an increase in tumour burden, associated with an increase in osteolytic bone lesions and elevated OPN expression in the bone marrow. Collectively, we show that metformin increases OPN expression in preosteoblasts, increasing myeloma cell adherence. In vivo, this translates to an unexpected indirect pro-tumourigenic effect of metformin, highlighting the importance of the interdependence between myeloma cells and cells of the bone microenvironment. |
format | Online Article Text |
id | pubmed-8665410 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-86654102021-12-21 The antidiabetic drug metformin acts on the bone microenvironment to promote myeloma cell adhesion to preosteoblasts and increase myeloma tumour burden in vivo Gámez, Beatriz Morris, Emma V. Olechnowicz, Sam W.Z. Webb, Siobhan Edwards, James R. Sowman, Aneka Turner, Christina J. Edwards, Claire M. Transl Oncol Perspective Multiple myeloma is a haematological malignancy that is dependent upon interactions within the bone microenvironment to drive tumour growth and osteolytic bone disease. Metformin is an anti-diabetic drug that has attracted attention due to its direct antitumor effects, including anti-myeloma properties. However, the impact of the bone microenvironment on the response to metformin in myeloma is unknown. We have employed in vitro and in vivo models to dissect out the direct effects of metformin in bone and the subsequent indirect myeloma response. We demonstrate how metformin treatment of preosteoblasts increases myeloma cell attachment. Metformin-treated preosteoblasts increased osteopontin (OPN) expression that upon silencing, reduced subsequent myeloma cell adherence. Proliferation markers were reduced in myeloma cells cocultured with metformin-treated preosteoblasts. In vivo, mice were treated with metformin for 4 weeks prior to inoculation of 5TGM1 myeloma cells. Metformin-pretreated mice had an increase in tumour burden, associated with an increase in osteolytic bone lesions and elevated OPN expression in the bone marrow. Collectively, we show that metformin increases OPN expression in preosteoblasts, increasing myeloma cell adherence. In vivo, this translates to an unexpected indirect pro-tumourigenic effect of metformin, highlighting the importance of the interdependence between myeloma cells and cells of the bone microenvironment. Neoplasia Press 2021-12-08 /pmc/articles/PMC8665410/ /pubmed/34890968 http://dx.doi.org/10.1016/j.tranon.2021.101301 Text en © 2021 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Perspective Gámez, Beatriz Morris, Emma V. Olechnowicz, Sam W.Z. Webb, Siobhan Edwards, James R. Sowman, Aneka Turner, Christina J. Edwards, Claire M. The antidiabetic drug metformin acts on the bone microenvironment to promote myeloma cell adhesion to preosteoblasts and increase myeloma tumour burden in vivo |
title | The antidiabetic drug metformin acts on the bone microenvironment to promote myeloma cell adhesion to preosteoblasts and increase myeloma tumour burden in vivo |
title_full | The antidiabetic drug metformin acts on the bone microenvironment to promote myeloma cell adhesion to preosteoblasts and increase myeloma tumour burden in vivo |
title_fullStr | The antidiabetic drug metformin acts on the bone microenvironment to promote myeloma cell adhesion to preosteoblasts and increase myeloma tumour burden in vivo |
title_full_unstemmed | The antidiabetic drug metformin acts on the bone microenvironment to promote myeloma cell adhesion to preosteoblasts and increase myeloma tumour burden in vivo |
title_short | The antidiabetic drug metformin acts on the bone microenvironment to promote myeloma cell adhesion to preosteoblasts and increase myeloma tumour burden in vivo |
title_sort | antidiabetic drug metformin acts on the bone microenvironment to promote myeloma cell adhesion to preosteoblasts and increase myeloma tumour burden in vivo |
topic | Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8665410/ https://www.ncbi.nlm.nih.gov/pubmed/34890968 http://dx.doi.org/10.1016/j.tranon.2021.101301 |
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